POS0914 LATE SKIN FIBROSIS IN SYSTEMIC SCLEROSIS: A STUDY FROM THE EUSTAR COHORT
Authors: M. Hughes, S. Huang, J. J. Alegre Sancho, P. Carreira, M. Engelhart, E. Hachulla, J. Henes, E. Kerzberg, M. R. Pozzi, G. Riemekasten, V. Smith, G. Szucs, M. Vanthuyne, E. Zanatta, O. Distler, A. Gabrielli, A. M. Hoffmann-Vold, V. Steen, D. Khanna
Journal: Annals of the Rheumatic Diseases (2022)

Background Skin fibrosis is a cardinal feature of systemic sclerosis (SSc) and associated with significant disability. The early trajectory of skin fibrosis provides insights into the course of the disease including mortality; however, little is known about late skin fibrosis in SSc. Objectives The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. Methods We developed and tested three conceptual scenarios of late (&gt;5 years after 1st non-RP sign or symptom) skin fibrosis (Figure 1): Figure 1. Conceptual models/scenarios of late skin fibrosis in SSc. A: worsening and then improvement (&gt;3 mRSS) during the first 5 years, and then worsened again after 5 years. B: worsening for the first time after 5 years. C: worsening in the first 5 years and stayed high after 5 years (i.e., failure to improve). A. Worsening and then improvement (&gt;3 mRSS) during the first 5 years, and then worsened again after 5 years. B. Worsening for the first time after 5 years. C. Worsening in the first 5 years and stayed high after 5 years (i.e., failure to improve). We defined skin worsening as modified Rodnan skin score (mRSS) ≥ 5 units or ≥ 25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19,115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1,043) patients who had limited (lcSSc) or diffuse cutaneous SSc (dcSSc) at baseline. Results One-fifth of patients among the whole cohort (n=208/1043, 19.9%) including in patients with lcSSc or dcSSc at baseline (n=193/887, 21.8%) developed late skin fibrosis. This was largely due to new skin worsening or failure to improve. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 antibodies (Table 1) were associated with progression from baseline lcSSc to dcSSc, and anticentromere antibodies were protective. Table 1. Impact of autoantibody status on progression from baseline limited to diffuse cutaneous SSc (dcSSc). Skin worsening after 5 years (Scenario B) (n=70 ) Skin worsening within 5 years and failed to improve after 5-year window (Scenario C) (n=61 ) Progressed to dcSSc (n=23 ) Not progressed to dcSSc (n=47 ) P-value Progressed to dcSSc (n=37 ) Not progressed to dcSSc (n=24 ) P-value Anticentromere +ve 2/22 (9.1%) 19/42 (45.2%) 0.0034 6/34 (17.6%) 14/21 (66.7%) 0.0002 -ve 20/22 (90.9%) 23/42 (54.8%) 28/34 (82.4%) 7/21 (33.3%) Anti-Scl-70 +ve 15/23 (65.2%) 14/44 (31.8%) 0.0088 22/36 (61.1%) 8/23 (34.8%) 0.0485 -ve 8/23 (34.8%) 30/44 (68.2%) 14/36 (38.9%) 15/23 (65.2%) Anti-RNA-Polymerase-III +ve 0/12 (0.0%) 1/22 (4.5%) 1.0000 0/6 (0.0%) 0/14 (0.0%) -- -ve 12/12 (100%) 21/22 (95.5%) 6/6 (100%) 14/14 (100%) Conclusion Late skin fibrosis affects approximately 20% of SSc patients &gt;5 years after onset of disease. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is usually due to new worsening or failure of skin to improve. Progression from baseline limited to diffuse cutaneous SSc was associated with anti-Scl-70 antibodies, and anticentromere antibodies were protective. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy. Acknowledgements On behalf of EUSTAR collaborators. Disclosure of Interests Michael Hughes Speakers bureau: Speaking fees from Actelion pharmaceuticals, Eli Lilly, and Pfizer, outside of the submitted work, Suiyuan Huang: None declared, Juan Jose Alegre Sancho Speakers bureau: Speaking and/or investigational fees from Actelion pharmaceuticals, Eli Lilly, Pfizer, Boehringer Ingelheim, Roche, and GSK, outside of the submitted work, Grant/research support from: Speaking and/or investigational fees from Actelion pharmaceuticals, Eli Lilly, Pfizer, Boehringer Ingelheim, Roche, and GSK, outside of the submitted work, Patricia Carreira: None declared, Merete Engelhart: None declared, Eric Hachulla Speakers bureau: Received consulting fees/meeting fees from Johnson &amp; Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme; speaking fees from Johnson &amp; Johnson, GSK, Roche-Chugai; and research funding from CSL Behring, GSK, Roche-Chugai and Johnson &amp; Johnson., Consultant of: Received consulting fees/meeting fees from Johnson &amp; Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme; speaking fees from Johnson &amp; Johnson, GSK, Roche-Chugai; and research funding from CSL Behring, GSK, Roche-Chugai and Johnson &amp; Johnson., Jörg Henes Speakers bureau: Lectures for CHUGAI, Boehringer-Ingelheim, Eduardo Kerzberg: None declared, Maria Rosa Pozzi: None declared, Gabriela Riemekasten: None declared, Vanessa Smith: None declared, Gabriella Szucs: None declared, Marie Vanthuyne: None declared, Elisabetta Zanatta: None declared, Oliver Distler: None declared, Armando Gabrielli: None declared, Anna-Maria Hoffmann-Vold: None declared, Viginia Steen: None declared, Dinesh Khanna Shareholder of: DK has stock options in Eicos Sciences, Inc., Consultant of: Consultant for Acceleron, Amgen, Boehringer Ingelheim, CSL Behring, Chemomab, Genentech/Roche, Horizon, Mitsubishi Tanabe Pharma, Prometheus, Talaris., Grant/research support from: Has received grants from Bayer, BMS, Horizon and Pfizer (to University of Michigan).